Methods of preparing alpha-amino acids and nu-substituted-alpha-amino acids



Patented Feb. 5, 1946 METHODS or rnarsamo "ammo acros AND N-SU'BSTITUTED-a-AMINO ACIDS John H. Biiiinan, Bioomington, Ind- No Drawing. Application September 19, 1941,

Serial No. 411

1 Claim (01. INF-581) This invention relates to methods of preparing a-amino acids and N-suhstituted-a-amino acids.

Amino acids have long been recognized as essential to biological processes in most living things and more recently have been utilized to sustain life. Numerous methods have heretofore been employed tor the synthesis or these amino acids and more particularly the a-amlno acids. For example, some oi these methods have been used which involve the amination of u-halogenated acids, the Gabriel synthesis and the Strecker synthesis. All of these methods, however, have the common disadvantage of being rather lengthy, expensive, and usually yielding small amounts of amino acids.

In accordance with this invention, a-amino acids and li-suhstituted-a-amino acids are prepared by a method which is eiilcient and economical. This method comprises protecting the amino group of p-amlno alcohol containing no aliphatic unsaturated group, oxidizing the protected 'fl-amino alcohol to the corresponding amino acid by converting its methylol group into a earboxyi group, and then removing the protecting group. This protection is achieved by re- 25 acting the p-amino alcohol with a compound containing a group which renders unoxidisable the amino radical of the p-amino alcohol during the oxidization or the methylol group of the alcohol to the carboxyl group. Desirably the compound which is reacted with the p-amino alcohol contains an acyl group. Examples oi "groups which protect the amino radical during oxidization oi the p-amino alcohol are: l

E l 2 (l) B- B- 3-- or RKC likil zone, toluene, o-xylene, dinitrobenzene, chlorobenzene, naphthalene, benzoic acid, and phenetole. Examples of compounds which contain the protecting group and which when reacted with the p-amino alcohol protect the amino radical during oxidization are aliphatic or aromatic acyl halides, anhydrides. esters, carboxylic acids and salts of the acids; aliphatic or aromatic sullonyl halides; aromatic or aliphatic aldehydes; aliphatic or aromatic dicarboxylic acid halides: aliphatic or aromatic dicarboxylic acid anhydrides: aliphatic or aromatic dicarboxylic acids and the salts at these acids; aliphatic or aromatic dicarboxylic esters; and aromatic or aliphatic suliocarboxylic acid halides, and aromatic or aliphatic suliocarboxylic acid anhydrldes. In the event that a salt of an aliphatic or aromatic acid, or aliphatic or aromatic dicarboxylic acid is used. the p-amino alcohol employed should be a salt or so the p-amino alcohol, such as the hydrochloride.

The reactions which take place in protecting the p-amino alcohol with the diflerent groups indicated in Formula 1 may be represented by the following equations:

rine, bromine or iodine, and R1 is hydrogen, an alkyl radical or an aryl radical containing no unsaturated aliphatic group and R4 is hydrogen.

an alkyl radical or an aryl radical containing no unsaturated aliphatic group.

and Z is a negative radical such as chloride.

tion may be performed by an eleotro-chemica! method. Preferably the reaction is perlormed between 0' c. and the boiling point or the reaction mixture.

3 i e The reactions which take place may be repre- 8 RPOEOE sented by the following equations:

(10) O R: in which Y is ehiorine. bromine. or iodine. n-tl-un-e Br-OHaOH k o n, e) n B: m t

n-lLnncoon -0 Mat-omen ---e n rt. (11) o n. B-d-N-iilh-OHNH B- NH- RFOHIOH 4- m 15 m E 0 B1 g B-l-NH-(Slh-cnon Bk NH:- BPO e u E 3| 8 E 3-6-N-4J3a-CEOH Rent B; H B 1z x-one-oxton n-d-N-dln-coon at E 8 1h (a) 0 a( \z-ont-omou n- 1t 8-0] R1 0 hf Mr--CHlOH 3o 3 CCl o o In B NIBtCOOH -Nn-d-omon E i B:\ R (14) 0 Bl o -NH- Bl-OHlOH mama 18 amt 0 H Bt-G HgOH it n. 1 R{O\O NHr-I-CHrOH -o 5 o R: 0 g NHi JR- 0l! o o C-NH0R !-0H E I B o N-hm-cmon 1 g R! 1d. 3 n o (JRCH,OH m2? The resulting protected p-amino alcoholisthen & oxidized to convert the methylol group of the 3 alcohol to a carboxyl group. This oxidation may 0 be performed by any suitable oxidizing agent, A n, such as: a. metallic permanganate, for example J an alkali-metal permanganate, an alkaline-earth 00 \g/ metal permanganate, or zinc permanganate, in an aqueous medium of any reaction, whether 9.1- g

kalineneutral; chrome 01mm!!! Sometimes the resulting product. instead of being a nt. including chromic aci 3- metallic an acid as indiented by Equations 10. 11, 12, 13, chromate and m a ic c ro s s 14, and 15, might be a salt of the acid, such as m dichmmatein an acid medium; an oxidlzthe sodium 8811;. A salt is formed it the oxidas acid. i e. in addition to the chromlc tion is performed in a basic medium, such as in acid already named, Feral-11mm! chlol'ic the presence of sodium hydroxide or sodium caracid, or nitric acid; lead peroxide; or ferric chlot ride: all of which oxidizing agents lie between 7 After the rotected fl-amino alcohol has been ferric chloride and Persulfufiv acid inclusive in oxidized to the corresponding acid, the resulting 183621680! oxidation-reduction potentials. (For ggmpound is degompgsed to form an -gmlno instance, see Oxidation potentials." by Lei-timer, acid. This decomposition may, for example, be published in New York by Prentiss-Hall, Inc.. in accomplished by hydrolyzlng the resulting oxida- 1938, pages 293 et seq.) Alternatively, the oxide.- tion compound with an acid, such as hydrochloric,

sulphuric, or nitric acid, or a base. such as sodium or barium droxide.

The ov reaction which takes place may be represented by the following equations:

i -Nn-dRP -oa marital-coon Typical examples of the method in accordance with this invention are as follows:

Example 1.Preparation of d-l-alcnine aminopropionic acid) Twenty grams of p-amino propyl alcohol are add to a solution containing 12 a. of sodium hydro do and 100 cc. of water. 38 g. of benzoyl chloride are added slowly in small portions, with stirring, to this mixture. The bennoyi derivative which is N-benzoyl-s-amino propyl alcohol separates out as an oil which crystallizes on standing. It may be represented by the foilowins formula:

(22) o x cm 43 g. of N-benzoyl-B-amino propyl alcohol are suspended in 100 cc. of water in a flask equipped with a mechanical stirrer. 50.6 g. of potassium permanganate are added to 500 cc. of water and the solution is stirred to form a saturated solution. Some of the potassium permanganate does not dissolve. The saturated solution of potassium permanganate is then added slowly through a dropping funnel over a period of minutes to the solution of N-benzcyl-p-amino propyl alcohol. The remaining potassium permanganate which is undissolved is then added in small portions as a solid to the reaction mixture The mixture is agitated for about half an hour after all the potassium permanganate has been added. The reaction mixtureis maintained at approximately room temperature. The manganese dioxide which is formed is filtered at and the filtrate is reduced in volume to about 200 cc. and acidified with dilute hydrochloric acid, such as GIN-hydrochloric acid. The N-benzoyl-u-amlno proprionic acid which is formed precipitates out. A small additional quantity of the N-benaoyLa-propicnic eanese dioxide with dilute sodium hydroxide. The crude N-bensoyl-s-amino propionic acid which is isolated is refluxed with 300 cc. of 26 percent hydrochloric acid (specific gravity 1.12) for about six hours. The nesultin: solution is cooled and the bensoic acid which is formed is filtered oil. The filtrate is evaporated to dryness and contains the hydrochloride of a-am-inopropionic acid. The residue is taken up in a small amount of warm water and an excess of pyridine is added followed by ten volumes of methyl alcohol. The pyridine reacts with the hydrochloride of the a-aminopropionic acid to produce a-aminopropionic acid. The -aminopropionic acid which is formed may be represented by the following formula:

(23) CHI Ten grams of s-amino isobutyl alcohol are added to cc. of water, with stirring. 5 e. of sodium hydroxide are added to the alcohol-water mixture. 26 g. of benzoic anhydride are then placed in a reaction mixture and the mixture stirred for a period of about six hours. The solid which precipitates out and which is N- benzoyl-B-amino isobutyi alcohol, is filtered. 5 g. of N-benzoyl-fl-amino isobutyl alcohol are suspended inlOO cc. of water. 15 cc. of concentrated sulfuric acid (specific gravity 1.83) are added. 12 g. of sodium dichromate are then added and the mixture heated nearly to boiling. It is then permitted to cool. A precipitate forms which is N-benzoyi-a-amino isobutyric acid. The solid material, which is filtered, is recrystallized twice from water. To 5 g. of the N-benzoyi-samino isobutyric acid are added 100 cc. of 20 percent hydrochloric acid and the mixture is refluxed for a period of six hours. After filtering oi! the benzoic acid, the filtrate is evaporated .to dryness and treated with aniline and alcohol to obtain the s-amino isobutyric acid.

Example 3.Preparoti0n of a-amino acetic acid Twenty grams of ethanolamine are benzoylated in the same manner as the p-amino propyl alcohol was benzoylated in Example 1 by employing 46 g. of benzoyl chloride. No attempt need be made to isolate the benzoyl derivative. The oxidation can be performed by adding to the reaction mixture 69.1 s. of potassium permanganate. The reaction may be maintained at a temperature of less than 10' ,C. during the addition of the permanganate. The solution is permitted to come up to room temperature before filtering oi! the manganese dioxide. The manganese dioxide is then filtered oil, the filtrate evaporated to 200 cc. and then acidified with concentrated hydrochloric acid. The N-benzoyl-a-amino acetic acid is refluxed with cc. of 1:1 hydrobromic acid for approximately three hours. The benzoic acid resulting from this hydrolysis is'fiitered oil. The c-amino acetic acid hydrobromide which is formed is converted to the c-amino acetic acid by treatment with a base in the manner described in Example 1.

Ezample 4.---l='repamti0n 0/ a-amino n-butvric acid Ten grams of N-benzoyi-p-amino n-butanol. prepared from p-amino butanoi and benzoyl chloride by a method analogous to that used in 1::-

acid may be obtained by extracting the manample l, are placed in 150 cc. of water. 24.8 I.

oilead peroxide and 100 cc. of slacial acetic acid are then added. The solution is refluxed overnight, filtered and evaporated to a small volume. 200 cc. of 20 percent H! are added and the solution refluxed for two hours. Upon cooling. the solid benxoic acid is removed and, the filtrate evaporated nearly to dryness. By the use oi pyridine and alcohol as described in Example 1, the s-amino butyric acid is isolated.

Erample 5.Preparation of s-amino isobutyric acid ' isobutyric acid.

Example ISL-Preparation of a-amino acetic acid Twelve grams of ethanol amine are dissolved in 100 cc. of water containing g. or sodium hydroxide. 45 g. or p-naphthalene sulionyl chloride are added and the mixture stirred. Upon acidification with hydrochloric acid, the naphthalene sulionamide separates out. Without further purification the amide is added to 100 cc. of water in which are dissolved 10 g. of sodium hydroxide. 33 g. of potassium permanganate are added to the mixture. Upon completion of the oxidation, the manganese dioxide is removed. The solution is then acidified to precipitate the N-naphthalene sultonyl derivative of a-amino acetic acid. This solidishydrolynedwith l50cc.oi20percentHCl for 12 hours. The mixture is filtered and evaporated to dryness. The residue istreatedwith alcohol and pyridine to isolate the -amino acetic sold in the manner described in Example 1.

Sample 7.Preparation of a-amino propionic acid Five grams of N-benzoyl c-amino n-propanol, prepared from bensoyl chloride and fi-amino npropanol similar to the method described in Example 1, are placed in 100 cc. of water containing 30.2 g. of ferric chloride. The mixture is stirred and heated to boiling. The solution is made basic upon' completion of the reaction and filtered. The filtrate, which contains the N-bensoyl cam'ino propionic acid is refluxed in the manner described in Example 1 to obtain the a-amino propionic acid.

Example 8.-Prepa1'ation of s-amino propionic acid Five grams of N-benzoyl p-amino n-propanol are suspended in 100 cc. of water to which are added 2.3 g. of potassium chlorate. 'Iwo cubic centimeters of concentrated sulfuric acid (95 percent) are added and the solution boiled for four hours. 100 cc. of 6 N HCl are added and the solution refluxed six more hours, cooled and filtered. The filtrate is evaporated and treated as in hxample 1 to obtain the u-amino acid.

Example 9.-Preparation Of s-amino acid p pi ni trated sulfuric acid percent) and the mixture refluxed for four hours. 100 cc. of 20 percent hydrochloric acid are added and the mixture refluxed six hours. Upon cooling the solution is filtered to remove the benzoic acid, evaporated and treated to isolate the a-amino propionic acid.

Example 10.Preparation of s-amino propionic acid Five grams oi N-benzoyl p-amino n-propanol are suspended in 50 cc. of water containing 5 cc. 0! concentrated sulfuric acid percent). 4.2 g. of chromic oxide (Cr 0:) are added and the mixture heated to boiling. The precipitate. N-henzoyl s-amino' propionic acid, which forms on standing, is recrystallized from water. This benzoylatcd amino acid is then hydrolyzed to obtain the e-amino propionic acid.

Example 11.Preparation oi a-amino n-butyric acid Ten grams oi p-amino n-butanol are dissolved in 50 cc. oi dry ether to which is added slowly 13 g. of isobutyryl chloride dissolved in ether and 18 g. of pyridine. The resulting isohutyryl amide is placed in cc. 0! water to which have been added 10 g. of sodium hydroxide. The solution is oxidized with potassium permanganate at from 5'40 C. with vigorous stirring. The manganese dioxide is removed and the filtrate acidified with 10 cc. of concentrated hydrochloric acid and refluxed for 10 hours. The solution is then evaporated down and filtered. The filtrate is evaporated to dryness and treated with pyridine and methyl alcohol to obtain the a-amino n-butyric acid.

Example 12.--Preparation of a-ammo acetic acid hours. The solution is then evaporated to dryness and treatedwith pyridine and methyl alcohol to obtain the a-amino acetic acid.

Brample 13.Preparaiion of a-amino acetic acid Fifty grams of succinic anhydride are added to an Erlenmeyer flask fltted with a ground glass loint and a variable take ofl condenser. To this mixture are added 33 a. of technical ethanol amine. A reaction follows immediately. The solution is then heated to C. and gradually raised to 172 C. on a Wood's metal bath. Reaction takes place and the water which is given oil is collected and removed. 20 g. of the resulting amide are oxidized. with potassium permanganate by first warming to 60 C. and then allowing the solution to stand overnight. Upon hydrolysis with 20 percent hydrochloric acid, the hydrochloride oi the s-amino acetic acid is obtained.

Increment-Preparation of a-amino acetic acid Seventy-four grams of phthalic anhydrlde are placedinanErlenmeyerflaskflttedwith avariable take of! condenser. To this mixture are added 34 g. of technical ethanol A viaorous reaction ensues within half a minute. The resulting solution is heated to HIP-150 C. for four hours and then gradually raised to 175 C. The water which formsv during the reaction is removed at the take oil. Upon cooling the reaction mixture solidifies. is removed from the fiask and washed thoroughly with water to remove excess ethanol amine. The precipitate is dried and has a melting point of 129-127 c.

To 20 g. oi" the above alcohol placed in sec cc. of water are added 22.6 g. of potassium permanas in Example 1 to free the amino acid.

Example 15.-Preparation of a-amino isobutrric acid Twenty grams of p-amino isobutanol are added to 50 cc. water containing 12 g. 0! sodium hydroxide. 24 g. of benzaldehyde are added. Heat is evolved and two layers formed. To this mixture are added 47.3 g. of potassium permanganate. Upon completion of the oxidation. the manganese dioxide is removed and the filtrate hydrolysed with hydrochloric acid and the solution evaporated to dryness: By treatment with. pyridine'and alcohol, the hydrochloride oi the amino acid is decomposed to liberate the amino acid. Example IL -Preparation of a-amino n-butyric Ten gram of finely divided N-henxoyl p-amino n-butanol are suspended in 500 cc: oi water containing cc. of concentrated suli'urlc acid (an. gr. 1.83). An electric current of 1.! amperes is passed through the solution for four hours during which time the solution is stirred vigorously. The oxygen set free at the anode oxidizes the N-bensoyl p-amino n-butanol to N-benxoyl a-amino n-butyric acid. The unreacted starting material (about 1 g.) is filtered oil and the solution reduced ,to about '15 cc. 'By treatment with percent hydrochloric acid the benzoyl group is removed from the N-benzoyl a-amino n-butyric acid. and the filtrate is evaporated to dryness as in Example 1, to obtain tree e-amlno n-butyric Example 17.Preparation o! t-smew mic ma Twenty grams of p-amino propancl are reacted with 12 g. o! acetaldehyde in the presence oi are refiuxed ior fifteen hours with 14.8 g. o! s-amino propanol during which time the alcohol is removed as it i'orms. At the end on! this time the solution is cooled, water is added, followed by a saturated solution containing 89 g. or calcium permanganate. The manganese dioxide which forms is removed by filtering. 20 percent hydrochloric acid is added and the solution reiluxed ior six hours at the end of which time the solution is evaporated to dryness under reduced pressure. An ethyl malonic acid left is removed with ether. The residue is treated with pyridine and methyl alcohol as in Example 1 to isolate the a-fllnlIlO propionic acid.

Example 19.-Preparation oj e-amino acetic acid Example 20.Preparatton of a-amine isobutyric acid To an ether solution or 2! g. or p-amino isobutanol is added the calculated amount 0! a-GhlOl'O sulfoacetyl dichloride solo dissolved in ether. The resulting precipitate is removed and the filtrate is oxidized with 82 g. 01' potassium permanganate and treated as in Example l to obtain the a-amino isobutyric acid.

As the foregoing examples show, the p-amino alcohols and the N-acyl-p-amino alcohols used are always primary alcohols; and so by the terms "p-amino alcohol and "N-acyl-p-amino alcohols" I mean such primary alcohols.

What is claimed is: 1. The method oi producing a composition selected'i'rom the class consisting of e-amino acids and lil-acyl-a-amino acids, which comprisesacylating the amino group or a p-amlno alcohol containing no aliphatic unsaturated group, and oxidizing the carbinol group of the resulting as N-acyl-s-amino alcohol to a carboxyl group by sodium hydroxide. To this solution are added trample 18. Preparation of a-amino propionic acid .Twentygramsoiethylmalonicester treating said last-named alcohol with an oxidizing agent lying between ferric chloride and Delsuliuric acid inclusive in the series oi oxidationreduction potentials.

2. Themethod of producing a composition selected from the class consisting of s-amino acids and N-acyl-e-amino acids, comprising oxidisins a s-amino alcohol containing no aliphatic unsaturated group and the amino group of which is acylated by treating said alcohol with an oxidizing agent lying between ferric chloride and per:- suli'uric acid inclusive in the series of oxidationreduction potentials.

8. The method oil producing e-amino acid. which comprises oxidising a. p-amino alcohol containing no aliphatic unsaturated group and the amino group of which isacylated by treating said alcohol with an oxidizing agent lying between ferric chloride and persuliuric acid inclusive in the series or oxidation-reduction potentials, and

hydrolysing the ruulting product to form an a-amino 001d.

4. The methcdot producing a composition selected from the class consisting oi a-amino acids and N-acyl-a-amino acids. which comprises reacting a compound containing an acyl group with a p-amino alcohol to form an N-acyl-p-amino alcohol, and oxidizing the carbinol group of said last-named alcohol to a carbonyl group by treating said last-named alcohol with an oxidizing agent lying between ferric chloride and persulturic acid inclusive in the series of oxidationreduction potentials.

5. The method of producing a-amino acid, which comprises reacting a compound containing an acyl group with a p-amino-alcohol to form an N-acyl-p-amino alcohol, oxidising the carhinoi group or said last-named alcohol to a carboxyl group by treating said last-named alcohol with an oxidizing agent lying between ferric chloride and per-sulfuric acid inclusive in the series of oxidation-reduction potentials, and hydrolysing the resulting product to form an a-amino acid.

6. In the method of producing a composition selected from the class which consists of a-amino acids and N-aeyl-a-amino acids, the step of oxidizing an N-acyl-p-amino alcohol by treatment of said alcohol with an oxidizing agent lying between ferric chloride and persulmric acid inclusive in the series of oxidation-reduction potentials.

'1. The method of producing a composition selected from the class which consists of a-amino acids and N-acyl-a-amino acids, which comprises oxidizing an N-bensoyl-p-amino alcohol by treating said alcohol with an oxidizing agent lying between ferric chloride and persuliurlc acid inclusive in the series of oxidation-reduction potentials.

8. The method of producing a composition selected from the class whichconsists oi u-amino acids and N-acyl-a-amino acids, which comprises Patent No. 2,394,230.

with reacting a composition containing a group with a p-amino alcohol to form an N- benzoyl-p-amino alcohol, and oaidising said N- bensoyI-p-amino alcohol to term at: N-benloyls-amino acid by' treating said alcohol with an oxidizing agent lying between ierris chloride and persuli'uric acid inclusive in the series oiozidaticn-reduction potentials.

9. In method oi producing a composition selected iron: the class which consists oi a-amino acids and N-aoyl-s-amino acids, the step or oxidining an N-acyl-p-amino alcohol by treating-it with potassium permanganate.

10. In the method of producing a composition selected from the class which consists of o-amino acids and N-acyl-a-amino acids, the step of oxidizing an N-acyl-p-amino alcohol by treating it awjith a chromic oxidizing agent in an acid me- 11. In the method oi producing a composition selected from the class which consists of a-amino acids and N-acyl-a-amino acids. the step of oxidieing an N-acyl-p tmino alcohol by treating it wietllil a metallic permanganate in an aqueous 111 um.

12. In the method of producing a compositionselected from the class which consists oi s-amino acids and lil-acyl-e-aminn acids, the step of 01idizing an liqacyl-p-amino alcohol by treating it an oxidizing acid.

13. In the method of producing a composition selected from the class which consists of a-amino acids and N-acyl-a-amino acids. the step of oxidizing an N-acyl-p-amino alcohol by treating it with nitric acid.

14. In the method oi producing a composition selected irom the class which consists of a-amino acids and N-acyl-a-am'ino acids. the step of oxidizing an N-acyl-p-amino alcohol by treating it with an alkali-metal dichromate in acid solution.

JOHN H. BIIIMAN.

. February 5,1946.

JOHN H. BILLMAN It is hereby certified that errors appear in thiiyrinted specification oi the above age 1, first column, line 20; after num patent correction as follows: "group 0 insert a; e 22, after co riding" strike out "6 and insert instead a-';' and .that the said Letters Patent that the same may conform to the record of the Signed and sealed this 30th day of April, A.

[ems] ould be read with this correction therein case in the Patent Oifice.

LESLIE FRAZER, Y

First Assistant Commissioner of Pm.

hydrolysing the ruulting product to form an a-amino 001d.

4. The methcdot producing a composition selected from the class consisting oi a-amino acids and N-acyl-a-amino acids. which comprises reacting a compound containing an acyl group with a p-amino alcohol to form an N-acyl-p-amino alcohol, and oxidizing the carbinol group of said last-named alcohol to a carbonyl group by treating said last-named alcohol with an oxidizing agent lying between ferric chloride and persulturic acid inclusive in the series of oxidationreduction potentials.

5. The method of producing a-amino acid, which comprises reacting a compound containing an acyl group with a p-amino-alcohol to form an N-acyl-p-amino alcohol, oxidising the carhinoi group or said last-named alcohol to a carboxyl group by treating said last-named alcohol with an oxidizing agent lying between ferric chloride and per-sulfuric acid inclusive in the series of oxidation-reduction potentials, and hydrolysing the resulting product to form an a-amino acid.

6. In the method of producing a composition selected from the class which consists of a-amino acids and N-aeyl-a-amino acids, the step of oxidizing an N-acyl-p-amino alcohol by treatment of said alcohol with an oxidizing agent lying between ferric chloride and persulmric acid inclusive in the series of oxidation-reduction potentials.

'1. The method of producing a composition selected from the class which consists of a-amino acids and N-acyl-a-amino acids, which comprises oxidizing an N-bensoyl-p-amino alcohol by treating said alcohol with an oxidizing agent lying between ferric chloride and persuliurlc acid inclusive in the series of oxidation-reduction potentials.

8. The method of producing a composition selected from the class whichconsists oi u-amino acids and N-acyl-a-amino acids, which comprises Patent No. 2,394,230.

with reacting a composition containing a group with a p-amino alcohol to form an N- benzoyl-p-amino alcohol, and oaidising said N- bensoyI-p-amino alcohol to term at: N-benloyls-amino acid by' treating said alcohol with an oxidizing agent lying between ierris chloride and persuli'uric acid inclusive in the series oiozidaticn-reduction potentials.

9. In method oi producing a composition selected iron: the class which consists oi a-amino acids and N-aoyl-s-amino acids, the step or oxidining an N-acyl-p-amino alcohol by treating-it with potassium permanganate.

10. In the method of producing a composition selected from the class which consists of o-amino acids and N-acyl-a-amino acids, the step of oxidizing an N-acyl-p-amino alcohol by treating it awjith a chromic oxidizing agent in an acid me- 11. In the method oi producing a composition selected from the class which consists of a-amino acids and N-acyl-a-amino acids. the step of oxidieing an N-acyl-p tmino alcohol by treating it wietllil a metallic permanganate in an aqueous 111 um.

12. In the method of producing a compositionselected from the class which consists oi s-amino acids and lil-acyl-e-aminn acids, the step of 01idizing an liqacyl-p-amino alcohol by treating it an oxidizing acid.

13. In the method of producing a composition selected from the class which consists of a-amino acids and N-acyl-a-amino acids. the step of oxidizing an N-acyl-p-amino alcohol by treating it with nitric acid.

14. In the method oi producing a composition selected irom the class which consists of a-amino acids and N-acyl-a-am'ino acids. the step of oxidizing an N-acyl-p-amino alcohol by treating it with an alkali-metal dichromate in acid solution.

JOHN H. BIIIMAN.

. February 5,1946.

JOHN H. BILLMAN It is hereby certified that errors appear in thiiyrinted specification oi the above age 1, first column, line 20; after num patent correction as follows: "group 0 insert a; e 22, after co riding" strike out "6 and insert instead a-';' and .that the said Letters Patent that the same may conform to the record of the Signed and sealed this 30th day of April, A.

[ems] ould be read with this correction therein case in the Patent Oifice.

LESLIE FRAZER, Y

First Assistant Commissioner of Pm. 

